A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice.

In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, profoundly lowers levels of TNF, interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either beta-adrenoreceptors or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone, azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored.

Varicella inoculation to prevent shingles, and cytomegalovirus inoculation to prevent cytomegalovirus associated graft failures.

I suggest varicella virus inoculation be considered to reduce the risk of herpes zoster (the shingles), and cytomegalovirus (CMV) inoculation be considered to reduce the risk of CMV associated transplant graft failure. Such inoculations are inexpensive and easy to implement, and are simple potential solutions to common and often severe medical problems with suboptimal current treatments.

Xenon as neuroprotectant in acute stroke?

Stroke is one of the most common diseases worldwide. A current focus of research is to find neuroprotectants that can be given during acute stroke. One specific target is to find antagonists of the N-methyl-D-aspartate (NMDA) receptor in an attempt to limit glutamate associated neurotoxicity. Xenon has recently been found to be an NMDA receptor antagonist. I suggest that xenon be considered as a neuroprotectant in acute stroke, and discuss methods of testing this proposal.

Monoamine oxidase inhibitors for IgA nephropathy.

IgA nephropathy (IgAN), characterized by renal mesangial deposits of antibodies (of the IgA subtype), is the most common glomerulonephritis worldwide. The cause of IgAN is not known. IgAN can often lead to end stage renal disease (ESRD), and there is no known treatment proven to prevent ESRD in IgAN. Long term use of steroids or other immunosuppressant drugs carry severe toxicities and other risks. IgAN patients have high serum levels of tumor necrosis factor-alpha (TNF). Increased monoamine levels, via increased cellular cyclic AMP, can decrease TNF elaboration. Monoamine oxidase inhibitors (MAO-Is) have been found effective in case studies for a number of diseases, e.g. rheumatoid arthritis and Crohn's disease, characterized by high TNF levels. Here I suggest that MAO-Is might be of utility in IgAN by decreasing TNF levels.

Last but not least.

When a simple rectangular grid is drawn toward one's face there is the striking illusion that a spherical bulge is protruding from the grid. This illusion may be helpful in studying the interaction of spatial and motion processing.

Alpha helix capping and the conformation of threonine.

The amino acid threonine contains two chiral carbons and thus can exist in four possible conformations. However, only a single conformation (2S, 3R) of threonine is incorporated in proteins by the cellular translation material. The conformation at the alpha carbon (carbon 2) is the same as that of the other amino acids in biological proteins, and there is no explanation for why this enantiomer was selected. Further, there is no explanation for the choice of conformation at the 3 carbon in threonine. Here, I suggest that the preferential ability of (2S, 3R) threonine over the (2S, 3S) enantiomer to participate in alpha helix capping interactions may have led to the selection of the (2S, 3R) conformation.

Cleidocranial dysostosis and the unity of the Homeric epics: an essay.

Numerous years ago, in this journal, Beasley diagnosed the character Thersites from Homer's Iliad with cleidocranial dysostosis. Additional evidence from the text is presented to support a diagnosis of cleidocranial dysostosis, and it is pointed out that this diagnosis may have implications in studying the question whether the two Homeric epics (the Iliad and the Odyssey) were composed by the same author.